1. Field of the Invention
The present invention relates to a system, method, and software arrangement for determining co-associations of allele types across consecutive genetic loci, permitting the haplotyping of genetic samples at one or more contiguous loci. The system, method, and software arrangement described herein can employ genotype data generated from a wide range of mapping methods to determine chromosomal haplotypes. As such, the system, method, and software arrangement of the present invention may be useful as an aid to the diagnosis and treatment of any disease which has a genetic component.
2. Background Information
Diploid organisms are those whose somatic cells contain two copies of each chromosome. Each of these two copies of a particular chromosome may be distinguished by the presence, within the DNA which comprises the chromosome, of certain genetic variations, which may include restriction fragment length polymorphisms (RFLPs), single nucleotide polymorphisms (SNPs), sequence tag sites (STSs), microinsertions, microdeletions, or variable numbers of tandemly repeated elements (VNTRs). Based on the presence or absence of particular polymorphisms at specific loci, chromosomes may be assigned to one of two “haplotypes,” the name used to refer to the collection of identifiable genetic features present on one of the two haploid chromosomes that are contained within the diploid set. In certain situations, particular haplotypes may be associated with the presence or absence of a particular mutation or other functional variation in specific genetic loci. Because these genetic variations or genotypes may be associated with certain disease states or even with predisposition to disease, determination of relationships between haplotypes and genotypes are of intense interest in genetic research.
One of the most difficult problems in determining haplotypes in diploid organisms is establishing the proper assignment of multiple polymorphic markers to the same chromosome. Thus, distribution of two different variants (or alleles) at two different genetic loci, for example A/a and B/b, could generate haplotypes AB, Ab, aB or ab depending upon the distribution of the two alleles between the two chromosomes. The problems of inferring diploid haplotypes through the use of population data have been extensively investigated and widely acknowledged. See Clark, 1990, Mol. Biol. Evol. 7:111-122; Excoffier and Slatkin, 1995, Mol. Biol. Evol. 12:921-927; Ma et al. 2000, Neural Computation 12:2881-2907; Gusfield, 2001, J. Computational Biology 8:305-323; Stephens et al., 2001, Am. J. Hum. Genet. 68:978-989; and Niu et al., 2002, Am. J. Hum. Genet. 70:156-169.